Variant chr18-3450206-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003244.4(TGIF1):c.-284A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,378,062 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 146 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 115 hom. )

Consequence

TGIF1
NM_003244.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.363

Variant links:

Genes affected

TGIF1 (HGNC:11776): (TGFB induced factor homeobox 1) The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]

TGIF1 links:

LOC124904237 (HGNC:):

LOC124904237 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 18-3450206-A-T is Benign according to our data. Variant chr18-3450206-A-T is described in ClinVar as [Benign]. Clinvar id is 1232556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGIF1	NM_003244.4 linkuse as main transcript	c.-284A>T		5_prime_UTR_variant	1/3	ENST00000343820.10
LOC124904237	XR_007066269.1 linkuse as main transcript	n.125+326T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGIF1	ENST00000343820.10 linkuse as main transcript	c.-284A>T		5_prime_UTR_variant	1/3	1	NM_003244.4	P1	Q15583-2

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3813

AN:

152140

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0856

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0210

GnomAD4 exome

AF:

0.00252

AC:

3087

AN:

1225804

Hom.:

115

Cov.:

AF XY:

0.00230

AC XY:

1358

AN XY:

591198

show subpopulations

Gnomad4 AFR exome

AF:

0.0858

Gnomad4 AMR exome

AF:

0.00780

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000244

Gnomad4 OTH exome

AF:

0.00646

GnomAD4 genome

AF:

0.0251

AC:

3829

AN:

152258

Hom.:

146

Cov.:

AF XY:

0.0246

AC XY:

1829

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0857

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.000863

Hom.:

Bravo

AF:

0.0279

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over